Network ethnopharmacological and molecular docking based evaluation of the anti-breast cancer activity for ayurvedic botanicals acting on hypoxia-inducible factor-1

Abstract

The recognized root causes of breast cancer aggressiveness, resistance to therapy, and poor prognosis encompass hypoxia-inducible factors (HIFs), the HIF-dependent cancer hallmarks angiogenesis and metabolic reconfiguration.There is enough evidence to suggest that HIF is involved in the progression of breast cancer.Information for the network was gathered from the following databases: Dr. Duke's, IMPPAT, PubChem, Binding DB, UniProt, and DisGeNET. The network was created using the Cytoscapeprogramme. Screened bioactives having similarity index more than 0.6 from polypharmacology approach were subjected to docking studies with HIF-1 (PDB ID: 1H2K) with PyRx software and the ligands with good docking score was further explored for molecular docking interaction analysis. The number of bioactives having interaction with HIF-1, equal to or greater than 0.6 from Ashwagandh, Shatavari, Neem, Alsi seeds, Methi, Haldi, Ghritkumari, Yashtimadhu, and KadiPatta was 12, 9, 2, 6, 12, 11, 5, 10, and 3, respectively. On performing the docking against the target HIF-1for top molecules with Araboglycyrrhizin (-10.1kcal/mol), Asparanin-A (-9.2 kcal/mol), Shatavarin-I (-9.2 kcal/mol), Shatavarin-X (-9.1 kcal/mol), Somniferanolide (-9.1 kcal/mol), Somniferawithanolide (-9.7 kcal/mol), Trigofoenoside-A (-9.2 kcal/mol), Trigofoenoside-F (-9.4 kcal/mol), Trillin (-9.9 kcal/mol), and Withanolide (-9.2 kcal/mol), the binding energies and molecular interactions of the ligands were fairly good as compared with standard synthetic ligand Acriflavine (-7.6 kcal/mol). The study elucidated an in silico molecular mechanism of HIF-1 inhibition by various bioactive phytoconstituents from selected plants. Comprehending the logic behind anti-breast cancer action was made easier with the help of experimental evidence of the network findings.